泊洛沙姆
体内
化学
光敏剂
结合
体外
细胞毒性
药代动力学
生物利用度
药物输送
药理学
色谱法
核化学
生物化学
有机化学
聚合物
共聚物
医学
生物技术
数学分析
生物
数学
作者
Joseph Cacaccio,Farukh A. Durrani,Ravindra R. Cheruku,Ballav Moni Borah,Manivannan Ethirajan,Walter A. Tabaczynski,Paula Pera,Joseph R. Missert,Ravindra K. Pandey
摘要
To determine the impact of delivery vehicles in photosensitizing efficacy of HPPH, a hydrophobic photosensitizer was dissolved in various formulations: 1% Tween 80/5% dextrose, Pluronic P-123 and Pluronic F-127 in 0.5%, 1% and 2% phosphate buffer solutions (PBS). HPPH was also conjugated to Pluronic F-127, and the resulting conjugate (PL-20) was formulated in PBS. Among the different delivery vehicles, only Pluronic P-123 displayed significant vehicle cytotoxicity, whereas Pluronic F127 was nontoxic. Compared to PL-20, HPPH formulated in Tween80 and Pluronic F-127 showed higher cell-uptake, but lower long-term retention in Colon26 cell compared to PL-20. The higher retention of PL-20 was similarly observed during in vivo uptake with BALB/c mice baring Ct26 tumors. In contrast to the in vitro uptake experiments, PL-20 showed slightly higher uptake compared to HPPH formulated in Tween or Pluronic-F127. A significant difference in pharmacokinetic profile was also observed between the HPPH-Pluronic formulation and PL-20. Under similar in vivo treatment parameters (drug dose 0.47 µmol kg-1 , light dose: 135 J cm-2 at 24 h post-injection of PS), HPPH formulated either in Tween or Pluronic F-127 formulation showed similar in vivo PDT efficacy (20-30% tumor cure on day 60), whereas PL-20 showed 40% tumor cure (day 60).
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